Calmodulin



Calmodulin (CaM) – calcium modulated protein – regulates various protein targets. It is used by various proteins as calcium sensor and signal transducer by binding to their calcium binding domain (CBD). It undergoes conformational change upon binding Ca++ via its 4 EF hand motives and can undergo post-translational modification. The images at the left and at the right correspond to one representative calmodulin, i.e. crystal structure of bovine brain Ca++ calmodulin in a compact form (1prw).

Maximum Occurrence of Calmodulin Conformations
Maximum Occurrence, a method for making rigorous numerical assessments about the maximum percent of time that a conformer of a flexible macromolecule can exist and still be compatible with the experimental data, was used to probe the conformational disorder of Calmodulin.



It was shown that the open (1cll) and closed (1prw) conformers can have MO of only 15% and 5% respectively.

Calmodulin in Motion
The clip represents Calmodulin in motion. At the beginning it is shown moving in the unbound form (ApoCaM), and it changes its conformation when Calcium ions are present in the medium (CaCaM).

/flash/Apo_CaM_CaCaM.swf

Motion of ApoCaM is elaborated on the basis of 23 conformations derived from NMR file 1cfc, using the 3D animation program Blender, and according to a system to be published soon (Zini et al., manuscript in preparation). The transition from ApoCaM to CaCaM is elaborated with Blender starting with conformation 21 of 1cfc to arrive in conformation 11 of pdb file 1x02.

Surface rendering is also elaborated using Blender, and shows the lipophilic potential as a scale of white-black and smooth-rough, form the most lipophilic to the hydrophilic. Electrostatic potential is represented as a series of lines moving in the direction Positive to Negative, elaborated according to a scheme to be published soon (Andrei et al., in preparation). As most lines are moving towards Calmodulin, one can learn that the protein is slightly acidic (negative partial charges on its surface).

This movie was created by Andrei, Zini et al., of the Scientific Visualization Unit, Institute of Clinical Physiology - CNR of Itlay.

Conformational change of Calmodulin



Unbound , Bound

3D Structures of Calmodulin
Update June 2011

Native CaM
1prw, 1deg – bCaM - bovine

1up5 – cCaM – chicken

1clm, 1osa, 1exr – PtCaM - Paramecium tetraurelia

3cln – rCaM - rat

1x02, 1dmo – XlCaM – NMR - Xenopus laevis

2k61, 2k0e – hCaM – NMR - human

1y6w, 1cll - hCaM

4cln – DmCaM - Drosophila melanogaster

1rfj – CaM – potato

1ooj – CaM – Caenorhabditis elegans

Mutant CaM
1ahr – cCaM (mutant)

2k0j, 1sw8 – hCaM (mutant) – NMR

apo CaM
1lkj – yapoCaM – NMR -yeast

1cfc, 1cfd - XlapoCaM – NMR

1qx5 – rapoCaM – rat

CaM N-terminal
2i08 - hCaM N-terminal (mutant)

1j7o, 1j7p - hCaM N-terminal – NMR

1f70 - XlCaM N-terminal – NMR

2ro8, 2roa - sCaM N-terminal+Ca – NMR - soybean

2ro9, 2rob - sCaM C-terminal+Ca – NMR

3ifk, 3b32 – rCaM N-terminal

1f54, 1f55 – yapoCaM N-terminal – NMR

CaM C-terminal
1f71 - XlCaM C-terminal – NMR

1cmg – bCaM C-terminal – NMR

1fw4 - bCaM C-terminal

1cmf – bapoCaM C-terminal – NMR

2hf5 - hCaM EF2 EF3 – NMR

2kxw – PtapoCaM + IQ motif of NAV1.2 – NMR

2kz2 – CaM (mutant) – chicken 2rrt – XlCaM (mutant)

CaM+ cations (not calcium)
2ksz – sCaM N-terminal+Mg – NMR

1ak8 - bCaM N-terminal+Ce – NMR

2eqc – XlCaM C-terminal+Mg– NMR

2pq3 – rCaM+Zn

2v01 – hCaM+Pb

2v02 – hCaM+Ba

1n0y – PtCaM+Pb

CaM small molecule complexes
3if7 – bCaM+sphingosylphosphorylcholine

1qiv, 1qiw – bCaM+DPDv

1a29, 1lin – bCaM+trifluoperazine

1ctr - hCaM+trifluoperazine

2kug, 2kuh - hCaM N-terminal EF1 EF2+halothane – NMR

2kdu – XlCaM+MUNC13-1 – NMR

1mux – XlCaM+W-7 – NMR

CaM complexed with protein CBD domains
3gp2 – cCaM+CaM kinase II δ chain

2dfs – cCaM+myosin 5A

2o5g – cCaM+ myosin light chain kinase peptide

2bcx – cCaM+ryanodine receptor 1 peptide

3gof, 2o60 – cCaM+nitric oxide synthase CBD

1niw - rCaM+nitric oxide synthase CBD

3bxk, 3bxl – rCaM+ calcium channel peptide

1g4y - rCaM+ potassium channel CBD

1qx7 – rapoCaM+potassium channel peptide

3hr4 - hCaM+nitric oxide synthase CBD

2x0g, 1yr5, 1wrz – hCaM+death-associated protein kinase 1 (DAP)

2kne – hCaM+PMCA C-terminal CBD

3ewt, 3ewv – hCaM+TNFR fragment

2w73, 2jzi, 2r28 – hCaM+Ser/Thr phosphatase CBD

3bya – hCaM+glutamate receptor peptide

3g43, 2vay, 2f3y, 2f3z, 2be6 – hCaM+calcium channel CAV1.2

3dve, 3dvj, 3dvk, 3dvm - hCaM+calcium channel CAV2.2

2k0f – hCaM+myosin light chain kinase peptide – NMR

1zuz – hCaM+DRP kinase peptide

1l7z – hCaM+CAP-23/NAP-22 CBD

1cdl - hCaM+CaM dependent kinase CBD

1iwq - hCaM+MARCKS CBD

2kn2 – sCaM C-terminal+NtMKP1 CBD – NMR

2k3s – CaM+smoothelin-like protein 1 – NMR

1cff - XlCaM+ calcium channel CBD - NMR

1sy9 – XlCaM+olfactory channel peptide

1nwd – XlCaM+glutamate decarboxylase CBD

1iq5 – XlCaM+CaM dependent kinase CBD

1ckk - XlCaM+CaM dependent kinase CBD - NMR

2ix7 – apoCaM+myosin-5A

2bbm, 2bbn - DmCaM+myosin light chain kinase

1mxe – DmCaM+rCaMKI CBD

2vas, 2vb6, 3gn4, 3l9i – DmCaM+myosin VI

2bki, 2bkh – CaM+myosin VI – pig

2fot - bCaM+α-II spectrin CBD

2f2o, 2f2p – bCaM+calcineurin CBD

1xa5 – bCaM+KAR-2

1cm1, 1cm4, 1cdm - bCaM+CaM dependent kinase CBD

2col, 1yrt, 1yru – BpCaM+adenyl cyclase – Bordetella pertussis

1zot – BpCaM C-terminal+adenyl cyclase

1xfu, 1xfv, 1xfw, 1xfx, 1xfy, 1xfz, 1y0v, 1sk6, 1pk0, 1lvc, 1k90, 1k93 - CaM+adenyl cyclase – Bacillus anthracis

2l1w – CaM+vacuolar calcium ATPase peptide – soybean – NMR

3oxq – hCaM + calcium channel Cav1.2

1qs7, 1qtx – CaM+RS20 – Escherichia coli

1vrk – CaM (mutant)+RS20

3ek4, 3ek7, 3ek8, 3ekh, 3ekj, 3evr, 3evu, 3evv, 3o77, 3o78 – CaM/DFP/myosin light chain kinase